2-Thiophenecarboxylic acid → US9296747, Example 13

HRID 930511Notes

Reaction equation

HRID 930511 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[C:33]([OH:35])=O.C(N(C(C)C)CC)(C)C.[CH3:45][O:46][C:47]1[CH:48]=[C:49]([NH:57][C:58]2[N:59]=[CH:60][C:61]3[CH2:67][NH:66][CH2:65][CH2:64][C:62]=3[N:63]=2)[CH:50]=[C:51]([O:55][CH3:56])[C:52]=1[O:53][CH3:54]>CN(C=O)C.CCOC(C)=O>[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[C:33]([N:66]1[CH2:65][CH2:64][C:62]2[N:63]=[C:58]([NH:57][C:49]3[CH:48]=[C:47]([O:46][CH3:45])[C:52]([O:53][CH3:54])=[C:51]([O:55][CH3:56])[CH:50]=3)[N:59]=[CH:60][C:61]=2[CH2:67]1)=[O:35]

Participants

7

Reactant 4

HCID 107002-Thiophenecarboxylic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 118970894N-(3,4,5-Trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 118970892US9296747, Example 13Yield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.021 g, 0.047 mmol) in anhydrous DMF (1.5 mL) was treated sequentially with thiophene-2-carboxylic acid (0.008 g, 0.062 mmol) and diisopropylethylamine (0.025 mL, 0.095 mmol). The reaction mixture was allowed to stir for 30 minutes at room temperature. After 30 minutes, N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine, Intermediate 1 (0.015 g, 0.047 mmol) was added to the reaction mixture. The reaction was allowed to stir for 3 hours at room temperature. The reaction mixture was then diluted with EtOAc and washed three times with brine. The combined aqueous layers were then washed twice with EtOAc. The organic layers were combined, dried over anhydrous Na2SO4(s), filtered and concentrated in vacuo. The crude product was then purified over silica using a MeOH/CHCl3 gradient affording the final product in 40% yield (0.008 g, 0.019 mmol).

Workup

  1. waitAfter 30 minutes
  2. stirringto stir for 3 hours at room temperature
  3. washwashed three times with brine
  4. washThe combined aqueous layers were then washed twice with EtOAc
  5. dry with materialdried over anhydrous Na2SO4(s)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was then purified over silica using a MeOH/CHCl3 gradient

Sources & evidence

ORD record
ord-07310bb424084d80a3723a8f641491e9
Source dataset
uspto-grants-2016_03
Patent number
US09296747B1

Reaction notes

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